The principal objective of this project is to determine the functional characteristics of the microvasculature of experimental brain tumors. The electron microscope is used to study the endothelium, with special emphasis upon the occurrence, frequency and distribution of fenestrations and other defects in the vascular wall. Light microscopic studies using serial section frozen histology are conducted to determine the permeability and distribution of horseradish peroxidase within experimental brain tumors. This compound, normally excluded from the mammalian brain functions as a histological marker of endothelial permeability, and is used in canine brain tumors to correlate images obtained by computed tomography. Quantitative autoradiography using the 14C compounds iodoantipyrine and aminoisobutyric acid are used, respectively, to determine blood flow and permeability. Correlation between horseradish peroxidase permeability and 14C-aminoisobutyric acid permeability, as imaged by the quantitative autoradiographic method are in progress. A double label method, with the capacity to simultaneously study permeability and blood flow is being developed and applied to multiple experimental brain tumor models induced in Fischer 344 rats. These modesl include tumor cell lines RG2, derived from an ENU rat glioma, S69-CL5, derived from an ASV-induced rat glioma and 9L, a gliosarcoma cell line derived from an MNU-induced rat tumor. These lines have been selected because of their morphological characteristics and their differential permeability characteristics which have been determined by our previous studies with horseradish peroxidase. Using quantitative autoradiographic methods, we can establish with accuracy the details of permeability and blood flow in our experimental tumors and develop methods to form a rational basis for studies designed to explore the uptake, distribution and effect of chemotherapeutic agents which may, ultimately, be useful in the treatment of spontaneous human gliomas.